In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8g/kg body weight, single injection) or chronic (1.6g/ kg body weight, 30days, biweekly injections) carbon tetrachloride ...

Poly(amido)amine (PAMAM) dendrimer G3 was investigated for its ability to support the proper functioning of rat heart mitochondria exposed to hyperglycemia, in both the in vitro and in vivo experiments. The main aims of this study were to check whether PAMAM G3 dendrimer improves the efficiency of the impaired respiration ...

Coenzyme Q(2) (CoQ(2)) is known to inhibit mitochondrial permeability transition pore (mPTP) opening in isolated rat liver mitochondria. In this study, we investigated and compared the effects of CoQ(2) on mPTP opening and ROS production in isolated rabbit heart and rat liver mitochondria. Mitochondria were isolated from New Zealand White ...

Rats use their vibrissal sensory system to collect information about the nearby environment. They can accurately and rapidly identify object location, shape, and surface texture. Which features of whisker motion does the sensory system extract to construct sensations? We addressed this question by training rats to make discriminations between sinusoidal ...

Insulin-like growth factor-I (IGF-I) is a powerful neuroprotective molecule in the brain and spinal cord. We have previously shown that intracerebroventricular (i.c.v.) IGF-I gene therapy is an effective strategy to increase IGF-I levels in the cerebrospinal fluid (CSF). Since aging in rats is associated with severe motor function deterioration, we ...

Here, the oxoglutarate carrier, already isolated from various sources and described in the literature, has been purified from rat brain and reconstituted in proteoliposomes for an accurate kinetic study. The rate of uptake of labelled oxoglutarate and malate has been measured in various conditions, essentially in double substrate experiments. The ...

Dichloroacetate (DCA) is a potential environmental hazard and an investigational drug. Repeated doses of DCA result in reduced drug clearance, probably through inhibition of glutathione transferase ζ1 (GSTZ1), a cytosolic enzyme that converts DCA to glyoxylate. DCA is known to be taken up by mitochondria, where it inhibits pyruvate dehydrogenase ...

A series of 2-(3-aryl-1-oxo-2-propenyl)-3-methylquinoxaline-1,4-dioxides 1a-l and 2-acetyl-3-methylquinoxaline-1,4-dioxide 2 were evaluated against Mycobacterium tuberculosis H(37)Rv. With the exception of the 4-nitro analog 1k, significant antitubercular potencies were observed in series 1 and 2 which have IC(50) values in the range of 1-23 microM. Negative correlations were noted between the IC(50) values ...

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus urinaria is widely used as anti-inflammatory, anti-diarrheal and hepatoprotective medicines in Asian countries such as India, China and Thailand. In Thailand, Phyllanthus urinaria is traditionally used as an adjuvant or alternative medicine for cancer patients, including liver cancer. However, there is limited scientific evidence supporting its use ...

Lead is a persistent and common environmental contaminant, which chiefly plays a significant role in modern industry. Coenzyme Q acts as electron and proton carrier in mitochondria and functions as an antioxidant in its reduced form (ubiquinol). To investigate the hazardous effects of lead on the coenzyme Q level, rats ...

This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human alpha-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, alpha-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting ...

Dehydroepiandrosterone (DHEA) is an important neurosteroid with multiple functions in the central nervous system including neuroprotection. How DHEA exerts its neuroprotection function has not been fully elucidated. One possible mechanism is via its active metabolites, 7alpha-OH DHEA and 7beta-OH DHEA. The purpose of this research is to understand how DHEA ...

Ecstasy, which is used as a recreational drug, is a common street name for 3, 4-methylenedioxymethamphetamine (MDMA). Another drug of abuse chemically related, though less common than MDMA, is the amphetamine derivative 4-methylthioamphetamine (MTA). MDMA and MTA induce different systemic and organ-specific effects, including neurotoxicity, hyperthermia, nephrotoxicity, cardiotoxicity and hepatotoxicity. ...

Male rats (21days) were assigned to enriched environment (EE) or to standard environment (SE) for 1year. Oxygen consumption and the sensitivity to calcium induced mitochondrial permeability transition (MPT), through mitochondrial membrane potential (DeltaPsi(m)) and swelling, were determined in isolated hippocampal and cerebral cortex mitochondria. Mitochondrial H(2)O(2) production rate, and NOS ...

The function of mitochondria in generation of cellular ATP in the process of oxidative phosphorylation is widely recognised. During the past decades there have been significant advances in our understanding of the functions of mitochondria other than the generation of energy. These include their role in apoptosis, acting as signalling ...

Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty acid unsaturation in rat liver. Mitochondrial ROS generation and the ...

The present study was designed with an aim to analyze the effect of acute aluminium phosphide (ALP) exposure (10mg/kg b.wt, intragastrically) on the kinetic characteristics of cytochrome oxidase and energy metabolism in male Wistar rat liver mitochondria. Liver mitochondrial preparations from ALP-treated rats exhibited significant decrease (66%) in the activity ...

Caspase-3 is one of the main executors of apoptosis. Its zymogen procaspase-3 was localized to cytosol, mitochondria and nuclei. The subcellular location of procaspase-3 in liver was reported by several studies to be either cytosolic or cytosolic and mitochondrial. Our aim was to investigate these separate procaspase-3 pools to differentiate ...

BACKGROUND AND OBJECTIVES: The mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca(2+) concentration [Ca(2+)](i) and the mitochondrial membrane ...

There is increasing evidence that the integrity of antioxidant defenses is of vital importance in extrahepatic cholestasis, particularly with regard to the functioning of the liver's mitochondria. Although the mechanisms by which cholestasis causes oxidant/antioxidant imbalance in mitochondria are poorly understood, hepatic injury caused by cholestasis may be due to ...

Preparations of rat liver mitochondria, but not of brain and heart mitochondria, produce large quantities of reactive oxygen species (ROS) in the presence of palmitoyl-CoA and other long-chain acyl-CoAs. Palmitoyl-CoA inhibited respiration of rat liver mitochondria with glutamate plus malate or with succinate as substrate. However, ROS production induced by ...

Data, both for and against the presence of a mitochondrial nitric-oxide synthase (NOS) isoform, is in the refereed literature. However, irrefutable evidence has not been forthcoming. In light of this controversy, we designed studies to investigate the existence of the putative mitochondrial NOS. Using repeated differential centrifugation followed by Percoll ...

Overoxidation and subsequent inactivation of Peroxiredoxin III (PrxIII), a mitochondrial H(2)O(2) scavenging enzyme, have been reported in oxidative stress conditions. No data are available in the literature about the presence of overoxidized forms of PrxIII in aged tissues. Liver mitochondria from 12-month-old rats and 28-month-old rats were here analyzed by ...

Retention of bile acids within the liver is a primary factor in the pathogenesis of cholestatic liver disorders, which are more common in human infants. The objective of this study was to evaluate developmental changes in mitochondrial factors involved in bile acid-induced hepatocyte injury. Hepatic mitochondria from adult rats (aged ...

To investigate the mitochondrial decay and oxidative damage resulting from aging, the activities/kinetics of the mitochondrial complexes were examined in the brains of young and old rats as well as in old rats fed R-alpha-lipoic acid plus acetyl-L-carnitine (LA/ALC). The brain mitochondria of old rats, compared with young rats, had ...

A series of experimental data points to the existence of profound diffusion restrictions of ADP/ATP in rat cardiomyocytes. This assumption is required to explain the measurements of kinetics of respiration, sarcoplasmic reticulum loading with calcium, and kinetics of ATP-sensitive potassium channels. To be able to analyze and estimate the role ...

In this study, we examined the relative efficacies of alpha-tocopherol, N-acetyl-serotonin, and melatonin in reducing ascorbate-Fe(2+) lipid peroxidation (LPO) of rat testicular microsomes and mitochondria. Special attention was paid to the changes produced on the highly polyunsaturated fatty acids (PUFAs) C20:4 n6 and C22:5 n6. The LPO of testicular microsomes ...

Indirubin, a red colored 3,2'-bisindole isomer, is a component of Indigo naturalis and is an active ingredient used in traditional Chinese medicine for the treatment of chronic diseases. The family of indirubin derivatives, such as indirubin-3'-oxime, has been suggested for various therapeutic indications. However, potential toxic interactions such as indirubin ...

Palmitate-induced uncoupling, which involves ADP/ATP and aspartate/glutamate antiporters, has been studied in liver mitochondria of old rats (22-26 months) under conditions of lipid peroxidation and inhibition of oxidative stress by antioxidants--thiourea, Trolox, and ionol. It has been shown that in liver mitochondria of old rats in the absence of antioxidants ...

Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST1. In the present study, we aimed to determine whether mtMGST1 also undergoes activation and about its function. When rats were treated with galactosamine/lipopolysaccharide ...

Acceleration of amyloid deposition by administration of amyloid fibrils and transmissibility of disease have been reported for several types of amyloidosis. Reactive amyloidosis (AA) occurs in a wide variety of domestic animal species and is characterized by amyloid deposition mainly in spleen, liver, and kidneys. Because the visceral organs of ...

36 leaves. Advisor: Dean A. Hoganson

BACKGROUND: The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Mitochondrial dysfunction represents a key factor in the progression of non-alcoholic steatohepatitis (NASH) as mitochondria are the main cellular site of fatty acid oxidation, ATP synthesis and reactive oxygen species (ROS) production. AIMS: (1) ...

A number of 3,5-bis(benzylidene)-4-piperidones 1 and some N-4-(2-aminoethoxy)phenylcarbonyl analogs 3-6 display excellent in vitro antimycobacterial properties. In particular, 1c and 6d are potent antimycobacterials which are well tolerated in mice and are identified as important lead molecules. The nature of both the benzylidene aryl rings and the terminal basic groups ...

Progressive decline of islet beta cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male ...

Hypotaurine is the precursor of taurine production from L-cysteinesulfinate. It is recognized that hypotaurine production in the liver occurs in cytosol. In the present study, hypotaurine production from L-cysteinesulfinate in rat liver mitochondria was investigated. The mitochondrial preparation prepared according to the method of Hogeboom and washed repeatedly with 0.25 ...

A series of carbamate derivatives of the H(3) antagonist ROS203 (1) were prepared, and their lipophilicity and steric hindrance were modulated by introducing linear or branched alkyl chains of various lengths. In vitro stability studies were conducted to evaluate how structural modulations affect the intrinsic reactivity of the carbamoyl moiety ...

We investigated the mechanism by which 3,5-diiodo-l-thyronine (T2) affects skeletal muscle mitochondrial bioenergetic parameters following its acute administration to hypothyroid rats. One hour after injection, T2 increased both coupled and uncoupled respiration rates by +27% and +42%, respectively. Top-down elasticity analysis revealed that these effects were the result of increases ...

Nonalcoholic fatty liver disease (NAFLD) has become common liver disease in Western countries. There is accumulating evidence that mitochondria play a key role in NAFLD. Nevertheless, the mitochondrial consequences of steatohepatitis are still unknown. The bioenergetic changes induced in a methionine- and choline-deficient diet (MCDD) model of steatohepatitis were studied ...

Phospholipids containing highly polyunsaturated fatty acids are particularly prone to peroxidation and membrane composition may therefore influence longevity. Phospholipid molecules, in particular those containing docosahexaenoic acid (DHA), from the skeletal muscle, heart, liver and liver mitochondria were identified and quantified using mass-spectrometry shotgun lipidomics in two similar-sized rodents that show ...

Extracts of Cimicifuga racemosa are used frequently for menopausal complaints. Cimicifuga is well tolerated but can occasionally cause liver injury. To assess hepatotoxicity of cimicifuga in more detail, ethanolic C. racemosa extract was administered orally to rats, and liver sections were analyzed by electron microscopy. Tests for cytotoxicity, mitochondrial toxicity ...

A liver-selective prodrug (3TCSD) of the antiviral drug lamivudine (3TC) was developed and characterized. 3TC was coupled to dextran ( approximately 25 kDa) using a succinate linker, and the in vitro and in vivo behavior of the conjugate was studied using newly developed size-exclusion and reversed-phase analytical methods. Synthesized 3TCSD ...

Autofluorescence response to oxygen supply modulation has been investigated in livers of rats under the hypermetabolic state associated to a pathological condition-hyperthyroidism-that is known to enhance hepatocyte metabolic activities involving both NAD, i.e. oxidative pathways engaged in ATP synthesis, and NADP, i.e. reductive bio-synthesis and antioxidant functions. Experiments have been ...

BACKGROUND: The role of Kupffer cells (KCs) in nonalcoholic steatohepatitis (NASH) which is regarded as a major cause of cryptogenic cirrhosis of the liver was investigated using stereological methods and electron microscopy in the rat model. To our knowledge, there is no stereological study on the volume of liver, total ...

Spontaneous apoptosis of T lymphocytes results in marked lymphopenia in the Biobreeding diabetes-prone (BB-DP) rat leading to the development of autoimmune type 1 diabetes. The lymphopenia phenotype in these rats is linked to the lyp locus. The lyp allele harbors a frameshift mutation within the gene encoding 'GTPase of immunity-associated ...

Cardiolipin (CL) is a unique phospholipid synthesised exclusively in the mitochondria where it is also mainly localised. Monolyso-CL acyltransferase is the enzyme responsible for re-acylating monolyso-CL to CL once a phospholipase A has removed one of the fatty acid tails. Because of CL's role in activating enzymes involved in energy ...

BACKGROUND: We have previously shown that chronic metabolic acidosis, induced in rats by NH(4)Cl feeding, leads to nephron hypertrophy and to a decreased water-salt reabsorption by the kidneys. Since mitochondria are the main source of metabolic energy that drives ion transport in kidney tubules, we examined energy-linked functions (respiration, electrochemical ...

It was recently demonstrated that the rat-selective toxicant norbormide also induces rat-selective opening of the permeability transition pore (PTP) in isolated mitochondria. Norbormide is a mixture of endo and exo stereoisomers; however, only the endo forms are lethal to rats. In the present study we tested both endo and exo ...

All-trans-retinoic acid (atRA) is incorporated covalently into proteins of rat testes mitochondria. In this study, the effect of three diets with different fatty acid composition on the retinoylation of proteins of rat testes mitochondria has been investigated. Different groups of rats were fed on a basal diet supplemented with 15% ...

Coenzyme Q (CoQ) has three well-characterized functions in mitochondria, namely (i) transfer of reducing equivalents in the electron transport chain, (ii) generation of superoxide anion radical, O2*-, and (iii) quenching of free radicals. The main purpose of this review is to discuss the effects of CoQ10 intake for relatively prolonged ...